1. Field of the Invention
The present invention relates to a drug-fluorophore complex for specific imaging of tumor cells only. More specifically, the present invention relates to a drug-fluorophore complex that can be used for the diagnosis of tumors during endoscopy, such as gastroscopy or colonoscopy (for example, the diagnosis of esophageal cancer and gastric cancer through a gastroscope, and colorectal cancer through a colonoscope), or minimally invasive surgery, such as laparoscopic or robotic surgery (for example, the diagnosis of cancers with peritoneal and lymph node metastases during laparoscopic surgery), in a rapid and simple manner.
2. Description of the Related Art
Changes associated with neoplasia are used to determine the diagnosis, treatment, and recurrence of tumors. Biomarkers have been most extensively studied in the diagnosis of tumors using changes associated with neoplasia. Many biomarkers have been proposed, but only a few thereof are reproduced in actual clinical practice. This is believed to be because the number of methods for diagnosing biomarkers expressed in some living cells in a simple manner within a short time is not sufficient. Heterogeneity in cancer tissue is responsible for the limited use of biomarkers. Different types of biomarkers are expressed at different levels from person to person in the same type of tumor (intertumoral heterogeneity) and even in a single tumor (intratumoral heterogeneity). However, such heterogeneities of tumors are not reflected in current diagnostic methods using biomarkers in small tissue sections. Thus, there is a need for a new method for detecting changes occurring in tumors while reflecting the heterogeneities of tumors.
Many efforts have been made to develop optical imaging systems and tumor-specific fluorophores for clinical applications (Troyan, S. L. et al. The FLARE intraoperative near-infrared fluorescence imaging system: a first-in-human clinical trial in breast cancer sentinel lymph node mapping. Ann. Surg. Oncol. 16, 2943-2952 (2009); Luker, G. D. & Luker, K. E. Optical imaging: current applications and future directions. J. Nucl. Med. 49, 1-4 (2008); Tromberg, B. J. et al. Assessing the future of diffuse optical imaging technologies for breast cancer management. Med. Phys. 35, 2443-2451 (2008)), and their potential applicability to imaging-guided diagnostic and surgical methods has been proposed in several preclinical studies (Kirsch, D. G. et al. A spatially and temporally restricted mouse model of soft tissue sarcoma. Nat. Med. 13, 992-997 (2007); von Burstin, J. et al. Highly sensitive detection of early-stage pancreatic cancer by multimodal near-infrared molecular imaging in living mice. Int. J. Cancer 123, 2138-2147 (2008)), and clinical studies (Sevick-Muraca, E. M. et al. Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore: feasibility study. Radiology 246, 734-741 (2008); Tagaya, N. et al. Intraoperative identification of sentinel lymph nodes by near-infrared fluorescence imaging in patients with breast cancer. Am. J. Surg. 195, 850-853 (2008); Stummer, W. et al. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol. 7, 392-401 (2006)). Particularly, non-invasive methods based on optical imaging are advantageous in that in vivo changes can be observed in real time and continuously, and possess other advantages of high sensitivity, fast measurement, and rapid imaging processing.
However, the technologies reported to date are generally associated with targeting to receptors specifically expressed in tumor cells, detection of low pH around tumors, or production of contrast agents targeting particular enzymes over-distributed around tumors. To the best of our knowledge, no attempts have been reported to specifically image tumors by taking advantage of the ability of drugs to penetrate tumor cells and non-tumor cells at different rates or levels.